Miniaturized Wireless Implantable Biosensors for Metabolic Monitoring

描述(申请人提供)：葡萄糖、乳酸、O2和二氧化碳的生理水平的变化可以提供代谢异常的早期迹象，这些代谢异常通常是随着肥胖导致的体重增加而进展的。虽然已经确定了一些与肥胖有关的代谢趋势，但与肥胖进展和相关疾病的发展相关的确切代谢物相互关系和复杂性还不是很清楚。此外，肥胖和相关的代谢变化似乎是患者特有的，这在很大程度上是没有调查的。众所周知，肥胖引起的代谢失衡会导致许多严重疾病的发展，包括糖尿病、心血管疾病、癌症和呼吸抑制。在过去的5年里，我们的团队一直在研究一种革命性的、完全可植入的生物传感器平台，能够连续监测血糖。这种微型(0.5x0.5x5 mm)传感器平台通过针插入皮下，并通过个人数字助理(PDA)设备进行远程操作。该传感器平台的关键部件之一是其涂层，它能够通过抑制炎症、纤维包裹和诱导新生血管生成来控制组织/植入物界面。这项拟议的研究旨在通过允许同时检测多个分析物(即葡萄糖、乳酸盐O2和二氧化碳)，在代谢监测方面取得巨大进步。将建立正常和肥胖大鼠在不同生物条件下(即喂食、禁食和轻度运动)这些分析物的趋势，以与我们建议的多分析物传感器进行比较。四个电化学传感器的紧密结合要求在设备集成方面取得更多进展。到拟议的三年研究结束时，将实现第一代多分析物传感器，并对涂层进行优化，以便在体内运行一个月。这种传感器有望实现新陈代谢监测的巨大飞跃，并将为该领域的研究人员提供调查肥胖及其相关疾病状态的复杂性的手段。小尺寸和低成本将提高患者的接受度和依从性，并将允许在正常的家庭环境中对大量患者进行更长时间的监测。这些数据将对该领域的研究人员非常有价值，以帮助理解肥胖的复杂性和患者特有的性质。此外，我们展望了这一多分析感官平台的未来集成，为糖尿病患者提供严密控制血糖水平的胰岛素/胰高血糖素闭环递送。

DESCRIPTION (provided by applicant): Variations in the physiological levels of glucose, lactate O2 and CO2 can provide an early indication of metabolic abnormalities that are usually progressive with weight gain associated with obesity. Although a number of metabolic trends related to obesity have been established, exact metabolite interrelationships and complexities as they pertain to obesity progression and the development of associated diseases are less well defined. In addition, obesity and associated metabolic changes appear to be patient-specific and this is largely uninvestigated. Metabolite imbalance resulting from obesity is known to lead to the development of a number of serious diseases including diabetes, cardiovascular diseases, cancer and respiratory depression. Over the past 5 years our team has been researching a revolutionary, totally implantable biosensor platform capable of continuously monitoring glucose. This miniaturized (0.5 x 0.5 x 5 mm) sensor platform is inserted subcutaneously through a needle and operated remotely through a personal digital assistant (PDA) device. One of the key components of this sensor platform is its coating, which is capable of controlling the tissue/implant interface by suppressing inflammation, fibrous encapsulation and inducing neo-angiogenesis. The proposed research intends to make a quantum-advance in metabolic monitoring by allowing simultaneous sensing of multiple analytes (i.e. glucose, lactate O2 and CO2). The trends of these analytes under various biological conditions (i.e. fed, fasting and light exercise) for normal and obese rats will be established for comparison with our proposed multi-analyte sensor. The close proximity of the four electrochemical sensors requires additional advances in device integration. By the end of the proposed three-year study, a first generation multi-analyte sensor will be realized along with coating optimization to permit one month in vivo operation. This sensor is envisioned to achieve a quantum leap in metabolic monitoring and will provide researchers in the field with the means to investigate the complexities of obesity and associated disease states. The small size and low cost will increase patient acceptance and compliance and will allow monitoring of large numbers of patients in a normal home environment and for extended periods of time. Such data will be extremely valuable to researchers in the field to assist in understanding the complexities and patient-specific nature of obesity. Moreover, we envision future integration of this multi-analyte sensory platform to provide closed-loop insulin/glucagon delivery for tight control of glucose levels in diabetic patients.